POS1470 POOR LONG-TERM OUTCOMES AND SUBSTANTIAL UNMET NEEDS IN EUROPEAN PATIENTS WITH LUPUS NEPHRITIS
Authors: L. Arnaud, J. MA, K. Pisarczyk, E. Park, K. Palaniswamy, R. Leff
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), associated with considerable morbidity and an increased risk of end-stage kidney disease (ESKD). Despite various therapies used in clinical practice, a notable proportion of patients may not achieve sustained remission, leading to adverse disease outcomes. <h3>Objectives</h3> To review and summarize evidence on natural history of LN, burden of comorbidities, and real-world (RW) effectiveness of therapy in European patients with LN. <h3>Methods</h3> A targeted literature review was conducted using MEDLINE/Pubmed and Embase to identify studies in patients with LN. Search strategies were developed for the two databases to identify relevant peer-reviewed articles published in English from March 2012 - March 2022, and conference abstracts from 2019. All records were screened according to pre-specified inclusion/exclusion criteria. Studies conducted in a European setting were summarized. <h3>Results</h3> Of 4,216 identified records, 55 studies reported long-term outcomes of disease and RW effectiveness of treatment in European adults with LN. Up to 36% of patients with SLE developed LN, and nearly all LN cases occurred within 5 years of SLE diagnosis. Patients with LN often suffered from serious infection (19-35%), chronic kidney disease (CKD)/ESKD (6-22%), and cardiovascular disease (CVD) (26%), and were more likely to experience cardio- and cerebrovascular events than patients with SLE only (p=0.001). Immunosuppressive therapies contributed to increased infections and patients treated with high-dose steroids (≥0.5mg/kg/day) had 5-times increased risk of infections compared to those on low-dose regimens. Patients with LN had a higher risk of mortality compared to patients with SLE or other lupus manifestations (p&lt;0.001). The main causes of death among patients with LN were infections (8-32%), CVD (22-58%), or malignancies (5-27%). The majority of RW studies evaluated effectiveness of standard of care (SOC) induction and/or maintenance therapy, mostly with mycophenolate mofetil and cyclophosphamide. Treatment response rates varied across the studies likely due to heterogeneity in study design, drug dosing, and patient population; comparative studies did not find significant differences in response rates between the regimens. Overall, 30-86% of patients with LN achieved complete renal response/remission (CRR) within 1 year of starting SOC therapy, and 25-63% achieved CRR within 2 years. Patients who were non-responders after 1 year had a significantly increased risk of mortality and CKD compared to responders (p&lt;0.005), highlighting the need to reach any degree of response. Over a 5-year period, one study reported that only 38% of patients maintained CRR while on SOC, further suggesting inadequate maintenance on existing therapies. Limited studies focused on treatment-experienced/refractory patients, with the majority evaluating rituximab (RTX)-based regimens. After 1 year of treatment, 29-64% of patients with refractory LN treated with RTX achieved CRR and 35% of patients with active LN despite SOC treated with belimumab (BEL) achieved CRR. Despite initial response to current therapies, 20-35% of patients experienced a renal relapse/flare while on maintenance therapy, with one study noting significantly increased risk of proteinuric flares with azathioprine compared to other maintenance therapies (p=0.01). Very limited evidence was identified on the impact of therapy on extra-renal manifestations in patients with refractory LN, with few studies reporting improvements in SLEDAI scores with RTX after 1 year and with BEL over 2 years of treatment. <h3>Conclusion</h3> European patients with LN have substantial burden from comorbidities that contribute to poor long-term outcomes. Treatment with SOC also contributes to increased morbidity and mortality, particularly due to infections. Furthermore, despite initial response to treatment, a notable proportion of patients experience renal relapse, indicating a need for effective therapies that provide sustained remission. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Laurent Arnaud Consultant of: Abbvie, Alexion, Alpine, Amgen, Astra-Zeneca, Biogen, BMS, Boehringer-Ingelheim, GSK, Grifols, Janssen, LFB, Lilly, Kezar, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB, Janice Ma Consultant of: Kezar Life Sciences, Inc., Konrad Pisarczyk Consultant of: Kezar Life Sciences, Inc., Eunmi Park Shareholder of: Kezar Life Sciences, Inc., Employee of: Kezar Life Sciences, Inc., Kiruthi Palaniswamy Shareholder of: Kezar Life Sciences, Inc., Employee of: Kezar Life Sciences, Inc., Richard Leff Shareholder of: Kezar Life Sciences, Inc., Consultant of: Kezar Life Sciences, Inc.